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Original article

HCV core gene polymorphisms correlate with liver fibrosis but not sustained virological response in patients with genotype 1 infection

Shih–Jer Hsu, Ching-Sheng Hsu, Chen-Hua Liu, Chun-Jen Liu, Chi-Ling Chen, Pei-Jer Chen, Ding-Shinn Chen, Jia-Horng Kao

Corresponding author name: Jia-Horng Kao
Corresponding author e-mail: kaojh@ntu.edu.tw

Citation: Antiviral Therapy 2011; 16:227-235
doi: 10.3851/IMP1741

Date accepted: 15 August 2010
Date published online: 03 March 2011

Abstract

Background: Amino acid (aa) substitutions in genotype 1 HCV core region (HCV-CR) serve as a negative predictor of treatment responses in Japanese chronic hepatitis C (CHC) patients. Whether this phenomenon could be extrapolated to non-Japanese patients remains unclear. We evaluated the effect of aa substitutions in HCV-CR on clinicopathological features and treatment responses in Taiwanese patients.

Methods: Clinical and serial virological data were collected from 147 consecutive Taiwanese HCV genotype 1 patients who received pegylated interferon plus ribavirin therapy. Quantification of HCV RNA and sequences of HCV-CR were determined by molecular methods.

Results: Of 147 patients, 90 (61.2%) attained rapid virological response (RVR) and 97 (66.0%) attained sustained virological response (SVR). Patients without aa substitutions in HCV-CR (coreWW) had a higher SVR than those with both aa70 and aa91 substitutions (coreMM; 70.5% versus 45.0%; P=0.039). Moreover, coreMM was associated with a higher γ-glutamyl transpeptidase level (P=0.026) as well as more severe liver fibrosis (P=0.027) than coreWW, and patients with aa70 substitution (coreMW) were associated with more severe liver steatosis and fibrosis than those without (P=0.020 and P=0.002, respectively). In multivariate analyses, lower pretreatment body mass index, milder liver fibrosis, 48 weeks of treatment and RVR, but not aa substitutions in HCV-CR, predicted a higher SVR rate.

Conclusions: Although aa substitution in genotype 1 HCV-CR is associated with more severe liver fibrosis and might be a negative predictor of SVR in Taiwanese CHC patients with interferon-based therapy, RVR and other clinical factors outweigh its role in predicting SVR.

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